PMID- 36708803
OWN - NLM
STAT- MEDLINE
DCOM- 20230328
LR  - 20230503
IS  - 2666-6367 (Electronic)
IS  - 2666-6367 (Linking)
VI  - 29
IP  - 4
DP  - 2023 Apr
TI  - Iron Overload Following Hematopoietic Stem Cell Transplantation: Prevalence, 
      Severity, and Management in Children and Adolescents with Malignant and 
      Nonmalignant Diseases.
PG  - 271.e1-271.e12
LID - S2666-6367(23)00044-1 [pii]
LID - 10.1016/j.jtct.2023.01.020 [doi]
AB  - Iron overload (IOL) is a frequently reported complication following hematopoietic 
      stem cell transplantation (HSCT) that has been investigated extensively in the 
      field of hemoglobinopathies but has not been thoroughly characterized after HSCT 
      in pediatric malignancies. Our aim was to assess prevalence, severity, risk 
      factors, and management of IOL, as defined using biochemical (serum ferritin) and 
      radiologic tools (T2*-weighted magnetic resonance imaging [MRI]), in a cohort of 
      pediatric patients who underwent HSCT for either malignant or benign diseases. 
      This monocentric, retrospective, observational study included all the 163 
      patients alive and in continuous remission at 24 months post-HSCT out of the 219 
      consecutive children and adolescents who underwent HSCT at our institution 
      between 2012 and 2018, were included in the study. IOL was classified into 4 
      categories: absent, mild, moderate, and severe. Among the 163 patients, 73% had 
      some degree of IOL (mild in 37%, moderate in 29%, and severe in 7%). 
      Moderate/severe IOL was more frequent among patients diagnosed with a malignant 
      disease versus those with a benign disease (43% versus 19%; P = .0065). Trend 
      lines for serum ferritin showed a "bell-shaped" distribution, with the highest 
      levels recorded during the first 6 months post-HSCT, followed by a spontaneous 
      reduction. Both pre-HSCT (1659 ng/mL versus 617 ng/mL; P < .001) and maximum 
      post-HSCT (2473 ng/mL versus 1591 ng/mL; P < .001) median ferritin levels were 
      statistically higher in the patients with malignancies. Radiologic assessment of 
      IOL confirmed a more severe degree in patients with malignant disorders compared 
      to those with benign disorders (median T2*-MRI, 4.20 msec [interquartile range 
      (IQR), 3.0 to 6.40 msec] versus 7.40 msec [IQR, 4.90 to 11.00 msec]; P = .008). 
      T2* levels were associated with the number of transfusions performed (P = .0006), 
      with a steeper drop in T2* values for the first 20 transfusions and a milder 
      slope for subsequent transfusions. T2* and ferritin values showed a statistically 
      significant negative exponential relationship (P < .0001), although a ferritin 
      level >/=1000 ng/mL showed poor specificity (48%) and low positive predictive value 
      (53%) for discriminating moderate-to-severe IOL from absent-mild IOL as assessed 
      by T2*-MRI, but with high sensitivity (92%) and negative predictive value (91%). 
      In a multivariable model, >20 transfusions (odds ratio [OR], 4.07; 95% confidence 
      interval [CI], 1.61 to 10.68; P = .003) and higher pre-HSCT ferritin level (P < 
      .001) were associated with the risk of developing moderate-to-severe IOL. Use of 
      a sibling donor (OR, .29; 95% CI, .10 to .77; P = .015) and a nonmalignancy (OR, 
      .27; 95% CI, .08 to .82; P = .026) were protective factors. Phlebotomy (66%), 
      low-dose oral chelators (9%), or a combined approach (25%) were started at a 
      median of 12 months after HSCT in 78% of the patients with IOL. Six percent of 
      the patients treated exclusively with phlebotomy (median, 14, significantly 
      higher in patients >40 kg) discontinued phlebotomy owing to poor venous access, 
      lack of compliance, or hypotension, whereas 39% of patients treated with 
      chelators developed mild renal or hepatic side effects that resolved after 
      tapering or discontinuation. Patients with malignancies showed statistically 
      higher pre-HSCT and post-HSCT ferritin levels and lower T2* values. High ferritin 
      level recorded on T2*-MRI showed unsatisfactory diagnostic accuracy in predicting 
      IOL; thus, T2*-MRI should be considered a key tool for confirming IOL after HSCT 
      in patients with an elevated serum ferritin level. IOL treatment is feasible 
      after HSCT.
CI  - Copyright (c) 2023 The American Society for Transplantation and Cellular Therapy. 
      Published by Elsevier Inc. All rights reserved.
FAU - Cattoni, Alessandro
AU  - Cattoni A
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; Dipartimento 
      di Medicina e Chirurgia, Universita degli Studi Milano-Bicocca, Milan, Italy. 
      Electronic address: alessandro.cattoni@unimib.it.
FAU - Capitoli, Giulia
AU  - Capitoli G
AD  - Dipartimento di Medicina e Chirurgia, Universita degli Studi Milano-Bicocca, 
      Milan, Italy; Centro B4 di Bioinformatica, Biostatistica e Bioimaging, Universita 
      degli Studi di Milano-Bicocca, Milan, Italy.
FAU - Casagranda, Sara
AU  - Casagranda S
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
FAU - Corti, Paola
AU  - Corti P
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
FAU - Adavastro, Marta
AU  - Adavastro M
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
FAU - Molinaro, Alessandro
AU  - Molinaro A
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
FAU - Di Gennaro, Filiberto
AU  - Di Gennaro F
AD  - Radiologia Diagnostica, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
FAU - Bonanomi, Sonia
AU  - Bonanomi S
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
FAU - Biondi, Andrea
AU  - Biondi A
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; Dipartimento 
      di Medicina e Chirurgia, Universita degli Studi Milano-Bicocca, Milan, Italy.
FAU - Galimberti, Stefania
AU  - Galimberti S
AD  - Dipartimento di Medicina e Chirurgia, Universita degli Studi Milano-Bicocca, 
      Milan, Italy; Centro B4 di Bioinformatica, Biostatistica e Bioimaging, Universita 
      degli Studi di Milano-Bicocca, Milan, Italy.
FAU - Balduzzi, Adriana
AU  - Balduzzi A
AD  - Pediatria, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; Dipartimento 
      di Medicina e Chirurgia, Universita degli Studi Milano-Bicocca, Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20230126
PL  - United States
TA  - Transplant Cell Ther
JT  - Transplantation and cellular therapy
JID - 101774629
RN  - 9007-73-2 (Ferritins)
RN  - 0 (Chelating Agents)
SB  - IM
MH  - Humans
MH  - Child
MH  - Adolescent
MH  - Retrospective Studies
MH  - Prevalence
MH  - *Iron Overload/diagnosis/epidemiology/etiology
MH  - Ferritins
MH  - *Precancerous Conditions/complications
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects/methods
MH  - Chelating Agents
OTO - NOTNLM
OT  - Childhood
OT  - Hemopoietic stem cell transplantation
OT  - Iron overload
OT  - Long-term transplantation-related complications
EDAT- 2023/01/29 06:00
MHDA- 2023/03/28 17:12
CRDT- 2023/01/28 19:24
PHST- 2022/11/13 00:00 [received]
PHST- 2023/01/05 00:00 [revised]
PHST- 2023/01/18 00:00 [accepted]
PHST- 2023/03/28 17:12 [medline]
PHST- 2023/01/29 06:00 [pubmed]
PHST- 2023/01/28 19:24 [entrez]
AID - S2666-6367(23)00044-1 [pii]
AID - 10.1016/j.jtct.2023.01.020 [doi]
PST - ppublish
SO  - Transplant Cell Ther. 2023 Apr;29(4):271.e1-271.e12. doi: 
      10.1016/j.jtct.2023.01.020. Epub 2023 Jan 26.